In recent years cosmetic compositions which improve the appearance of skin have become popular with consumers. There is, at the present time, a demand for cosmetic compositions which reduce the appearance, i.e., the outward indications or signs, of cellulite.
Cellulite is a lay term describing the uneven texture of skin in specific areas of the female body, primarily the hips, thighs, and buttocks. The prevalence of cellulite is high, estimated between 50% and 80% of the female population. Virtually no cellulite has been observed in men with normal androgen levels. The severity of cellulite tends to worsen with obesity, although it is easily observable in women with a below average body mass index, as well as with age, although postmenopausal women report a reduction in cellulite.
Premenopausal females tend to store fat subcutaneously, primarily in the gluteal/thigh areas where cellulite is most common. The elevation in androgen levels postmenopausally results in a dramatic shift in fat storage patterns. Fat is stored in the visceral and subcutaneous depots of the abdomen, more similar to male fat storage patterns, explaining the reduction in cellulite symptoms of postmenopausal women. Triglyceride is stored in individual adipocytes which are grouped into capillary rich lobules. Thin, vertical septa of connective tissue separate the lobules and tether the overlying superficial fascia to the underlying muscle.
The dimpling/bumpy appearance of cellulite is a result of the deformation of the aforementioned lobules as a result of outward forces on the adipose tissue (e.g., muscle flexing resulting in a localized outward pressure, pull of gravity). These lobules are large (up to 1 cm wide) and easily protrude into the overlying dermis, causing a visible deformation on the surface of the skin that presents itself as cellulite. As the connective septa run in the same direction as these outward forces, they can offer no counter force to keep the adipose from deforming into the dermis.
Net fat storage or removal within the adipocyte is dependent on a balance between uptake of dietary triglycerides circulating in the blood via chylomicrons and breakdown of stored triglyceride within the adipocyte and removal of free fatty acids for subsequent energy utilization. Lipolysis (breakdown of triglyceride within the adipocyte), occurs when hormone sensitive lipase (HSL) is activated. HSL activation requires phosphorylation via a cAMP (cyclic adenosine monophosphate) dependent protein kinase. As such, cAMP level is rate limiting to lipolysis. Net level of cAMP is a result of a balance between its enzymatic synthesis from adenosine triphosphate (ATP) via adenylate cyclase and its breakdown via phosphodlesterases. Adipocytes express both beta and alpha-2 receptors, which both activate and inactivate, respectively, adenylate cyclase.
Most cellulite treatments focus on lipolysis as the primary mode of action. Soudant et al. (U.S. Pat. No. 5,194,259) teach anti-cellulitis composition using an alpha-2 blocker, theoretically stimulating lipolysis. A number of patents cite use of xanthines (e.g., caffeine and derivatives) as phosphodiesterase inhibitors (French Patent No. 2,499,405; French Patent No. 2,554,344; Marissal et al., U.S. Pat. No. 4,684,522; Trebose et al., U.S. Pat. No. 5,030,451). Unfortunately, these products have not had great success in the marketplace, presumably due to poor efficacy. This may be a result of the fact that caffeine and xanthines in general have very limited solubility in water and the drug's activity in a typical cosmetic preparation (e.g., oil in water emulsion) would be very low due to poor penetration as it is bound in a crystallized form in the product.
Alpha hydroxy acids are emerging as accepted ingredients for improving the appearance of dry, flaky, wrinkled, aged, photodamaged skin and for treating various disorders of skin, e.g., hyperkeratosis, ichthyosis, skin blemished, acne, warts, herpes, psoriasis, eczema, pruritis. See e.g., U.S. Pat. No. 4,234,599 (Van Scott et al.), U.S. Pat. No. 4,612,331 (Barratt et al.), U.S. Pat. No. 4,424,234 (Alderson et al.), U.S. Pat. No. 4,839,161 (Bowser et al.).
The use of inositol phosphoric acid compounds in skin treatment compositions is also known, albeit to a much lesser extent. For example, U.S. Pat. No. 5,268,176 (Znalden et al.) discloses the topical application of an inositol phosphoric acid for treatment of a dermatological condition commonly known as spider veins. U.S. Pat. No. 5,116,605 (Alt) dicloses compositions including phytic acid (also known as "inositol hexaphosphate") for mitigating male pattern baldness and testosterone-induced acne. DE 4242876 (Beiersdorf) discloses cosmetic compositions containing citric acid, biotin, and phytic acid as an anti-oxidant.
The use of xanthines, e.g., caffeine and/or theophylline, in cosmetic compositions is also known, particularly as lipolytic agents for cellulite treatment. For instance, U.S. Pat. No. 5,215,759 (Mausner) discloses anti-cellulite compositions based on a specific combination of five ingredients and which may optionally include caffeine and sodium lactate. U.S. Pat. No. 5,362,494 (Zysman et al.) discloses cosmetic compositions containing xanthines as liporegulators and hydroxy acids, in particular glycolic acid, as a deplgmenting agent. U.S. Pat. No. 5,037,803 (Guyene et al.) discloses cosmetic compositions which may include theophylline or caffeine and lactic acid. Compositions containing an inositol phosphoric acid described in the above-cited Znaiden et al. '176 patent may also include xanthines.
The art discussed above does not envision a method of reducing the appearance of cellulite by increasing the strength and firmness of epidermal and dermal layers of the skin, which in turn results in an increased support for the underlying tissue. Rather, the anti-cellulite art focuses on the treatment of cellute via lipolysis. Additionally, the transdermal delivery of xanthines and, consequently, their efficacy, is limited by their poor solubility in aqueous-based or ethanol-based cosmetic compositions, and the art discussed above does not address the need for solubilizing xanthines and does not envision skin treatment compositions based on a specific combination of a xanthine with an alpha hydroxy acid or an inositol phosphoric acid according to the present invention.
Accordingly, it is an object of the present invention to provide a method of reducing the appearance of cellulite by applying to cellulite-affected skin ingredients for treating layers of skin tissue above subcutaneous fat.
It is an object of the present invention to provide skin treatment compositions containing a solubilized xanthine in a water-based or water/solvent-based mixture.
It is another object of the invention to provide compositions containing an alpha hydroxy acid in combination with a xanthine.
It is yet another object of the invention to provide compositions containing an inositol phosphoric acid in combination with a xanthine.
It is still another object of the invention to provide a method for preventing or reducing the appearance of cellulite by applying to the skin a composition containing a xanthine in combination with an inositol phosphoric acid and/or an alpha hydroxy acid.
It is another object of the present invention to provide a method of reducing the appearance of cellulite by applying to cellulite-affected skin a composition containing a combination of an inositol phosphoric acid and an alpha hydroxy acid.
These and other objects of the invention will become more apparent from the detailed description and examples that follow.